Study linking high maternal weight to elevated 5-HT in offspring draws mixed reactions

29 Nov 2022 --- Maternal weight may significantly contribute to adverse neurobiological effects in offspring, according to new research from Duke University, NC. The study focuses on how a maternal high-fat diet causes endotoxin accumulation in fetal tissue, with subsequent inflammation causing sex-specific neuropsychiatric disorders.

“Bulk sequencing from a large cohort of matched first-trimester human samples reveals sex-specific transcriptome-wide changes in placental and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content),” says the study.

Reactions from experts have been mixed. Responses attack the study’s lack of data regarding the diet of the studied mothers, as well as how the studied data came from terminated fetuses, thereby providing no opportunity for further study. Others point out how such a pathway could offer a potential path for future research.

“There is no data on any of the mother’s diet in this study, and because the research nature of the study, it was undertaken on fetuses which came from terminated pregnancies, there is no information of how children develop or grow, and therefore the effect of this observation on child and adult mental health is not known,” says Dr. Duane Mellor, registered dietitian and senior teaching fellow at Aston Medical School.

Reactions to the study largely point to lack of substantial data to support its findings. Raised 5-HT levels
The study, published in Nature Metabolism, highlights how male offspring exposed to a high-fat maternal diet specifically exhibited excess 5-TP, a neurotransmitter associated with poor mental health.

“Fetal brain 5-HT levels decrease as placental triglycerides increase in male mice and male human samples,” says the study. “These findings uncover a microglia-dependent mechanism through which maternal diet can impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.”

Experts in the field were quick to react, especially to the linking of maternal weight to 5-TP levels. 

“These studies suggest that feeding fat in mice and levels of fat moving through a human placenta can affect cells making 5-HT,” Mellor underscores.

“5-HT is a neurotransmitter associated with poorer mental health, including depression and anxiety. However, some studies have suggested it may be the brain’s response to the environment, more than levels of 5-HT, which could be the problem.”

“There is not a definitive link between the findings of this study and how levels of fat passing through the placenta may impact mental health and well-being,” he remarked.

Mellor points out additional flaws in the argument on a broader level and stresses that the study does not provide data on how diets in humans may influence mental health. 

“There is no data linking the weight of a human mother to their child’s well-being and mental health. It is important that any person living with a higher body weight should not be stigmatized and supported to achieve the best physical and mental health they can, and this must include mothers and their children if we are going to improve the health of our communities,” he concludes. 

He argues that the study’s claim on weight relationships may cause societal damage.

Potential usesThe study reveals that increased maternal weight may cause detrimental effects on male offspring.
Other critics are more willing to see the study’s merits, if only for its potential in future applications. 

“Epidemiologists have long pointed to strong associations between maternal diet and the characteristics of her offspring,” says Professor Neena Modi, professor of neonatal medicine at Imperial College London.

“However, it’s been hard to demonstrate cause and effect, and we need this before we can implement effective policies to break the damaging consequences of poor diet in pregnancy. Identifying the actual biological mechanisms is also essential to identifying possible drug targets.”

Modi highlights that the researchers may have identified a valuable pathway for further parallel study.

“This controlled mouse study indicates a causal relationship between maternal high fat diet and neurobehavioural effects in offspring, and it identifies a biological pathway. The parallel exploration in human tissue suggests similar findings and opens an approach to identify possible therapeutic targets,” she concludes. 

A similar recent study linked body mass index with decreased brain function among children. 

By James Davies